A study investigating the efficacy and safety of copanlisib versus placebo inpatients with rituximab-refratory indolent non-Hodgkin's lymphoma.
- Conditions
- Rituximab-refractory indolent non-Hodgkin's lymphomaMedDRA version: 19.0Level: PTClassification code 10029600Term: Non-Hodgkin's lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2014-000925-19-IT
- Lead Sponsor
- BAYER HEALTHCARE AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 189
1. Ability to understand and willingness to sign written informed consent. Signed informed consent must be obtained before any study specific procedure.
2. Histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to the following: o Follicular lymphoma (FL) grade 1-2-3a. o Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 109/L at the time of diagnosis and at study entry. o Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM). o Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal).3. Patients must have received two or more prior lines of treatment. A previous regimen is defined as one of the following: at least two months of single-agent therapy, at least two consecutive cycles ofpolychemotherapy, autologous transplant, radioimmunotherapy.4. Prior therapy must include rituximab and alkylating agent(s). Prior exposure to idelalisib or other PI3K inhibitors is acceptable provided thatthere is no resistance.5. Patients must be refractory to the last rituximab-based treatment (no response or response lasting < 6 months).6. Patients must have at least one bi-dimensionally measurable lesion (which has not been previously irradiated) according to the Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification.
7. Patients affected by WM, who do not have at least one bi-dimensionally measurable lesion in the baseline radiologic assessment, must have measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level = 2 xupper limit of normal (ULN).8. Male or female patients = 18 years of age.9. ECOG performance status = 1.10. Life expectancy of at least 3 months.11. Availability of fresh (preferred) and/or archival tumor tissue at Screening.12. Women of childbearing potential and men must agree to use adequate contraception when sexually active. This applies since signing of the ICF until at least 3 months after the last study drug administration. The investigator or a designated associate is requested to advise the patient how to achieve an adequate birth control. Adequatecontraception is defined in the study as any medically recommend method (or combination of methods) as per standard of care.13. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days before start of study treatment: o Total bilirubin = 1.5 x ULN (= 3 x ULN for patients with Gilbert-Meulengracht syndrome or for patients with cholestasis due to compressive adenopathies of the hepatic hilum). o Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)= 2.5 x ULN (= 5 x ULN for patients with liver involvement of their lymphoma). o Amylase and lipase = 1.5 x the ULN
o Glomerular filtration rate (GFR) = 30 ml/min/1.73 m2 according to theModification of Diet in Renal Disease (MDRD) abbreviated formula. o International normalized ratio (INR) and partial thromboplastin time (PTT) = 1.5 x ULN.Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring is recommended according to the local standard of care. o Platelet count = 75,000/mm3. o Hemoglobin (Hb) = 10 g/dL. o Absolute neutrophil count (ANC) = 1500/mm3.14. Lef
1. Previous assignment to treatment during this study. 2. Close affiliation with investigational site.3. Histologically confirmed diagnosis of FL grade 3b.4. Chronic lymphocytic leukemia.5. Transformed disease: o histological confirmation of transformation, or o clinical and laboratory signs: rapid disease progression, high standardized uptake value (>12) by positron emission tomography at baseline if PET scans are performed.6. Previous/concurrent cancer that is distinct in primary site/histology from indolent B-cell NHL within 5 yrs before start of study treatment except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta, Tis and T1].8. Bulky disease o Lymph nodes/tumor mass (except spleen) =7cm LDi (longest diameter).11. Known lymphomatous involvement of the central nervous system.12. Congestive heart failure > NYHA class 2.
13. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 mths). Myocardial infarction less than 6 mths before start of study treatment.14. Uncontrolled arterial hypertension (systolic blood pressure >150mmHg or diastolic blood pressure >90mmHg despite optimal medical management).15. Type I/II diabetes mellitus with HbA1c >8.5% or fasting plasma glucose >160mg/dL at Screening.16. Arterial or venous thrombotic or embolic events such as cerebrovascular accident, deep vein thrombosis or pulmonary embolism within 6 mths before start of study treatment.17. Non-healing wound, ulcer, or bone fracture.18. Active clinically serious infections > CTCAE Grade 2.19. Known history of HIV infection.20. Hepatitis B or C. All patients must be screened for HBV and HCV up to28 days before start of study treatment using the routine hepatitis virus laboratory panel. Patients positive for HBsAg or HBcAb will be eligible if negative for HBV-DNA. Patients positive for HCV IgG will be eligible if negative for HCV-RNA.21. Patients with seizure disorder requiring medication.22. Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event = CTCAE Grade 3 within 4 wks before start of study treatment.23. Renal failure requiring hemo- or peritoneal dialysis.24. Proteinuria as measured by urine protein/creatinine ratio >3.5 on a
random urine sample.25. History/concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function.26. Concurrent diagnosis of phaeochromocytoma.27. Pregnant/breast-feeding patients. Women of childbearing potential must have a serum pregnancy test performed a max. of 7 days before start of study treatment, and a negative result must be documented before start of study treatment.28. Unresolved toxicity > CTCAE Grade 1 attributed to any prior therapy/procedure excluding alopecia and = CTCAE Grade 2 peripheral neuropathy.29. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.30. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.31. Any illness/medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.33. Treatment with investigational drugs within 28 days before start of study treatment.34. Ongoing immunosuppressive therapy.35. Radiotherapy or immuno/chemotherapy within 4 wks before start of study treatment.36. Radioimmunotherapy/autol
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method